Anticoagulation with heparin is intrinsic to virtually every procedure involving vascular injury or vascular manipulation, such as arterial bypass or angioplasty. Heparin,a polydisperse, sulfated polysaccharide possesses numerous other biological activities, including the ability to inhibit smooth muscle cell proliferation. Cationic protamine, has been used since 1939 to reverse heparin induced anticoagulation, but protamine therapy is frought with severe complications including exacerbation of smooth muscle cell proliferative lesions at sites of vascular injury. It is our assertion that a world-wide market exists for a safe protamine replacement which in principal, will specifically neutralize heparin' s conventional. anticoagulant properties without causing deleterious side- effects. Commonwealth Biotechnologies, Inc. (CBI) has developed four lead compounds which display high affinity for anticoagulant heparin which function in vivo to neutralize heparin's anticoagulant effects. In Phase I, we will continue to optimize the structures of our lead compounds and demonstrate their efficacy in vitro and in vivo. Their effect on smooth muscle proliferation and their usefulness in physiologically relevant surgical situations will be examined. These studies will form the basis for expanded and continued work in Phase II.